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A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease

Authors :
Johanna Störmer
Wilfried Gwinner
Katja Derlin
Stephan Immenschuh
Song Rong
Mi-Sun Jang
Nelli Shushakova
Hermann Haller
Faikah Gueler
Robert Greite
Source :
Biomedicines, Vol 10, Iss 5, p 1198 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Nephrotoxic drugs can cause acute kidney injury (AKI) and analgesic nephropathy. Diclofenac is potentially nephrotoxic and frequently prescribed for pain control. In this study, we investigated the effects of single and repetitive oral doses of diclofenac in the setting of pre-existing subclinical AKI on the further course of AKI and on long-term renal consequences. Unilateral renal ischemia–reperfusion injury (IRI) for 15 min was performed in male CD1 mice to induce subclinical AKI. Immediately after surgery, single oral doses (100 mg or 200 mg) of diclofenac were administered. In a separate experimental series, repetitive treatment with 100 mg diclofenac over three days was performed after IRI and sham surgery. Renal morphology and pro-fibrotic markers were investigated 24 h and two weeks after the single dose and three days after the repetitive dose of diclofenac treatment using histology, immunofluorescence, and qPCR. Renal function was studied in a bilateral renal IRI model. A single oral dose of 200 mg, but not 100 mg, of diclofenac after IRI aggravated acute tubular injury after 24 h and caused interstitial fibrosis and tubular atrophy two weeks later. Repetitive treatment with 100 mg diclofenac over three days aggravated renal injury and caused upregulation of the pro-fibrotic marker fibronectin in the setting of subclinical AKI, but not in sham control kidneys. In conclusion, diclofenac aggravated renal injury in pre-existing subclinical AKI in a dose and time-dependent manner and already a single dose can cause progression to chronic kidney disease (CKD) in this model.

Details

Language :
English
ISSN :
10051198 and 22279059
Volume :
10
Issue :
5
Database :
Directory of Open Access Journals
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
edsdoj.bac626924948462bb6fbfd6a5c3a0223
Document Type :
article
Full Text :
https://doi.org/10.3390/biomedicines10051198